Background: Oral submucous fibrosis (OSMF) is a progressive disorder that causes mucosal stiffness, pain, burning sensation, and restricted mouth opening. Intralesional corticosteroids are commonly used, while platelet-rich plasma (PRP) has emerged as a regenerative treatment. Aim: To compare intralesional triamcinolone acetonide and PRP in improving mouth opening and relieving symptoms in patients with OSMF. Materials and Methods: This prospective comparative study included 20 patients with Grade II or III OSMF. Patients were equally allocated to receive weekly intralesional injections of triamcinolone acetonide or autologous PRP for two months. Mouth opening, pain, and burning sensation were assessed at baseline, one week, three weeks, and two months. Data were analysed using the independent-samples t-test and repeated-measures ANOVA. Results: Both treatments significantly improved mouth opening, pain, and burning sensation over time (p < 0.001). At two months, mouth opening was greater in the triamcinolone group than in the PRP group (29.50 ± 1.08 versus 27.50 ± 1.08 mm; p = 0.001). PRP produced greater reductions in pain (1.20 ± 0.42 versus 4.20 ± 0.63) and burning sensation (1.50 ± 0.53 versus 4.30 ± 0.48) at two months (both p < 0.001). Conclusion: Triamcinolone was more effective in improving mouth opening, whereas PRP provided greater relief from pain and burning sensation.